Disulfide hydrogels, based on cysteine-driven redox systems, exhibit remarkable self-assembly properties through reversible disulfide bond formation, making them a promising platform for dynamic material design.
A research team from IRG-2, led by Prof. Joseph Patterson and Prof. Douglas Tobias, employed advanced cryogenic electron microscopy (cryo-EM) to reveal a consistent fiber diameter of 5.4 nm. Using these structural insights, the team conducted all-atom molecular dynamics (MD) simulations with cryo-EM-informed constraints, successfully replicating fiber structures that closely matched experimental observations. Simulated cryo-EM images further validated these findings. The simulations showed that the disulfide gelator (CSSC) predominantly adopts an open conformation, with hydrogen bonding playing a key role in stabilizing the fibers. Notably, intermolecular interactions peaked at 70% conversion to the disulfide gelator, rather than at full conversion (100%), in alignment with previous unrestrained simulations. This suggests that the thiol precursor (CSH) helps stabilize the transient phase, highlighting the crucial interplay between CSH and CSSC in the assembly process.
These findings offer new insights into molecular self-assembly mechanisms and provide strategies for designing tunable materials through controlled assembly conditions. Learn More
Song Y, Li Z, Mulvey J, Freites JA, Patterson J, Tobias DJ. Cryo-EM Informed Molecular Dynamics Simulations to Investigate the Disulfide Hydrogel Self-Assembly. Chemphyschem. 2025 Mar 3:e202401085. doi: 10.1002/cphc.202401085. Epub ahead of print. PMID: 40032615.
This work has been published in ChemPhysChem. The research team included collaborators from CCAM Yuanming Song, Zhaoxu Li, Joseph Patterson and Douglas Tobias.